BioTraces Inc. has developed the proprietary Multiple Photon Detection (MPD) technique that permits detection and quantitation of target substances down to the sub-zeptomole/ml level using sub-license amounts of selected radioisotopes. Furthermore, MPD permits discrimination of co- resident labels, so that simultaneous quantitation of several target molecules is possible (multicolor). We demonstrated the advantages of the 1st generation of MPD instruments in a plurality of biomedical applications. We developed MPD enhanced chromatographic methods (HPLC/MPD and TLC/MPD) which achieved sub-attomole/sample sensitivity. MPD enhanced immunoassays (SIRMA) demonstrated a few hundred-fold better sensitivity than ELISA. MPD enhanced quantitative PCR (qPCR/MPD) permits quantitation of nucleic acids at the few copies level. MPD offers great advantage for the direct detection of nucleic acid. We are currently developing the MPD based methods for proteomics. The aims of this proposal are to develop a family of MPD devices based on the new generation of position sensitive photomultiplier tubes. Using these devices up to 16-fold higher throughput may be achieved leading to the ability to concurrently image a full 384 well microtiter plate. This will permit the applications of supersensitive MPD enhanced methods to high throughput applications in medical diagnostics, life sciences and pharmaceutical R&D. PROPOSED COMMERCIAL APPLICATIONS: Detection of biological substances at ultra-low levels is becoming increasingly important in life science research, clinical diagnostics and drug discovery. In all of these applications high throughput is an essential element, particularly for drug discovery applications, where the number of drug target/drug candidate pairs is growing exponentially. The high throughput ultrasensitive detector to be developed herein will become a major tool in these high value applications.